| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
We have clarified that most of cortical neurons temporary positioned in the subventricular zone (SVZ) as multipolar cells during the radial migration. But the biological meaning of this process has not been addressed. The observations that the multipolar cells extend the axon like process oriented orthogonal to the direction of the migration led us to a hypotheses that this step would be required for acquiring the environmental cues to determine the direction of the axon extension. In this view, we had screened the receptor molecules expressed in the SVZ, and identified 15 genes. Among them, ten genes had been already known to be involved in axon-guidance in other system. We further examined the functions of one of the candidates, Robo2, on the multipolar cells. In situ hybridization revealed that Robo2 mRNA was expressed in the SVZ and intermediate zone (IZ) on embryonic day 15.5 (E15.5), and also in the cortical plate (CP) on E16.5 onward. On the other hand, the Robo2 protein was observed only in the IZ, especially on the axon bundles on E16.5 using immunohitochemistry. This discrepancy between the distribution of mRNA and protein suggests that the Robo2 protein is transported into the axon of the migrating neurons before entering the CP. The fact that the repulsive ligand, Slit1, is known to be expressed in the deeper portion of the CP in this stage hinted the working hypothesis as below. Robo2 is located in whole cell-body in the multipolar cells so that the multipolar cells are prevented to enter the CP by the repulsive signal of Slit1 from the CP. After the establishment of axonal process on the multipolar cells, the Robo2 protein is transported into the axon and withdrawn from the cell-body. This transport enables the migrating neurons to enter the CP. We observed that the over-expression of Robo2 caused the delay of migration, consisting with this hypothesis.
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